The proposed project will investigate the role of lymphocyte and monocyte cell surface differentiation antigens in the mediation and modulation of Human T and B cell immune effector functions in health, autoimmune disease, and lymphoproliferative states. The long-term goals of this project are (a) to physically separate and functionally characterize subpopulations of Human lymphocytes and monocytes on the basis of presence of stable differentiation antigens, and to define their immune effector and regular roles, (b) to identify pathophysiologically relevant immunoregulatory abnormalities in patients with auto-immune and lymphoproliferative malignant diseases and (c) to develop non-toxic modes of therapy to correct these abnormalities. Reagents to be used are 13 monoclonal lymphocyte hybrid antibodies produced using the cell fusion technique of Kohler and Milstein. Four of these monoclonal antibodies are T cell specific (3A1, 5A12, 7E6, and 5E9) while one (4F2) is monocyte specific. After characterization of the monoclonal antibodies and the cell surface antigens to which they bind, the monoclonal antibodies will be used to physically separate subpopulations of lymphocytes and monocytes for functional studies. In vitro assays of immunoregulatory T cell function will include (a) T cell help and suppresseion of B cell immunoglobin synthesis, (b) T cell cytotoxicity against a variety of cellular targets, (c) tritiated thymidine incorporation after stimulation of lymphocytes by mitogens or antigens, and (d) T cell mediation of the autologous and allogeneic mixed lymphocyte reaction. In vitro assays of monocyte function will include induction and suppression of B cell immunoglobulin synthesis and monocyte mediated cytotoxicity. After indepth study of normal immunoregulatory control mechanisms, immunoregulatory control mechanisms will be studied in a variety of autoimmune disease (eg systemic lupus erythematosis), hypersensitivity reactions (eg Cogan's syndrome) and lymph proliferative states (EB virus induced infectious mononucleosis and B cell lymphomas). Finally, the effect of in vivo and in vitro immunoregulatory pharmacologic agents such as cortico-steroids, azathroprine, cyclophosphamide and indomethacin on the number and function of immunoregulatory cell subsets will be studied.